68 Participants Needed

PEP-CMV + Nivolumab for Brain Cancer

(PRiME II Trial)

Recruiting at 2 trial locations
EM
Overseen ByEric M Thompson, M.D.
Age: < 65
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Washington University School of Medicine
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should not be on certain immunosuppressive agents or tumor-directed therapies. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the PEP-CMV + Nivolumab treatment for brain cancer?

Research suggests that targeting cytomegalovirus (CMV) antigens, which are present in glioblastoma (a type of brain cancer), can help the immune system recognize and kill cancer cells. This approach has shown promise in using the body's immune response to fight glioblastoma, indicating potential effectiveness for treatments like PEP-CMV.12345

Is the combination of PEP-CMV vaccine and Nivolumab safe for humans?

Nivolumab (also known as Opdivo) is generally considered safe, but it can cause immune-related side effects, such as colitis (inflammation of the colon), which may require treatment with steroids. The PEP-CMV vaccine is still being studied, and while it shows promise in boosting immune responses, its safety profile in humans is not fully established yet.678910

What makes the PEP-CMV + Nivolumab treatment unique for brain cancer?

The PEP-CMV + Nivolumab treatment is unique because it targets cytomegalovirus (CMV) antigens, which are present in glioblastoma (a type of brain cancer) but not in normal brain tissue, allowing the immune system to specifically attack the cancer cells. This approach combines a vaccine targeting CMV with Nivolumab, an immune checkpoint inhibitor, to enhance the immune response against the tumor.12111213

What is the purpose of this trial?

This is a multisite, phase I/II clinical trial in children and young adults with newly-diagnosed high-grade glioma (HGG), diffuse midline glioma (DMG) and recurrent HGG/DMG, Medulloblastoma (MB), or ependymoma (EPN) to determine the safety, immunogenicity, and efficacy of a CMV-directed peptide vaccine plus checkpoint blockade.

Research Team

EM

Eric M Thompson, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for children and young adults with new or recurrent high-grade gliomas, diffuse midline gliomas, medulloblastoma, or ependymoma. Participants must meet specific health criteria to ensure safety during the trial.

Inclusion Criteria

My cancer has spread to other parts of my body.
My bone marrow is functioning well.
Patients must be able to understand and sign an IRB approved written informed consent document
See 15 more

Exclusion Criteria

Patients with active unrelated systemic illness
I am currently undergoing treatment specifically for my tumor.
Pregnant or breast-feeding women
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive temozolomide and PEP-CMV vaccine during the induction cycle

11 weeks
Multiple visits for drug administration and monitoring

Maintenance Treatment

Participants continue to receive PEP-CMV vaccine every 28 days until recurrence or progression

Until progression
Monthly visits for vaccine administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 years

Treatment Details

Interventions

  • Nivolumab
  • PEP-CMV vaccine
Trial Overview The study tests a CMV-directed peptide vaccine (PEP-CMV) combined with Nivolumab, an immune checkpoint inhibitor. It also includes Temozolomide chemotherapy and a Tetanus booster to enhance the immune response.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Phase II: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental Treatment4 Interventions
Cycle 1 (Induction cycle) is 77±2 days. Will receive 1 course of temozolomide 200 mg/m\^2/day x 5 days on Days 1-5 of cycle 1 \& receive PEP-CMV vaccine at dose level 1 (250 μg/m\^2) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days until recurrence/progression. Patients will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine delivered 6-24 hours prior to the first vaccine on day 21. Patients will also receive nivolumab 3 mg/kg IV on day 14±1 day then every 14 days ±2 days thereafter.
Group II: Phase I Stratum III: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental Treatment4 Interventions
Patients with recurrent/progressive MB or EPN with measurable disease can be enrolled at any point following recurrence regardless of any prior therapy. Cycle 1 (Induction cycle) is 77±2 days. Will receive 1 course of temozolomide 200 mg/m\^2/day x 5 days on Days 1-5 of cycle 1 \& receive PEP-CMV vaccine at dose level 1 (250 μg/m\^2) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days until recurrence/progression. Patients will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine delivered 6-24 hours prior to the first vaccine on day 21. Patients will also receive nivolumab 3 mg/kg IV on day 14±1 day then every 14 days ±2 days thereafter.
Group III: Phase I Stratum II: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental Treatment4 Interventions
Patients with recurrent/progressive HGG or DMG with measurable disease can be enrolled at any point following recurrence regardless of any prior therapy. Cycle 1 (Induction cycle) is 77±2 days. Will receive 1 course of temozolomide 200 mg/m\^2/day x 5 days on Days 1-5 of cycle 1 \& receive PEP-CMV vaccine at dose level 1 (250 μg/m\^2) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days until recurrence/progression. Patients will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine delivered 6-24 hours prior to the first vaccine on day 21. Patients will also receive nivolumab 3 mg/kg IV on day 14±1 day then every 14 days ±2 days thereafter.
Group IV: Phase I Stratum I: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental Treatment4 Interventions
Patients with newly-diagnosed high-grade glioma or DMG may be enrolled any time within 42 days after completing radiation. Cycle 1 (Induction cycle) is 77±2 days. Will receive 1 course of temozolomide 200 mg/m\^2/day x 5 days on Days 1-5 of cycle 1 \& receive PEP-CMV vaccine at dose level 1 (250 μg/m\^2) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days until recurrence/progression. Patients will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine delivered 6-24 hours prior to the first vaccine on day 21. Patients will also receive nivolumab 3 mg/kg IV on day 14±1 day then every 14 days ±2 days thereafter.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

🇺🇸
Approved in United States as Opdivo for:
  • Advanced or metastatic gastric cancer
  • Gastroesophageal junction cancer
  • Esophageal adenocarcinoma
  • Melanoma
  • Non-small cell lung cancer
  • Renal cell carcinoma
  • Hodgkin lymphoma
  • Head and neck squamous cell carcinoma
  • Urothelial carcinoma
  • Colorectal cancer
  • Hepatocellular carcinoma
  • Esophageal squamous cell carcinoma
🇪🇺
Approved in European Union as Opdivo for:
  • Melanoma
  • Non-small cell lung cancer
  • Renal cell carcinoma
  • Hodgkin lymphoma
  • Head and neck squamous cell carcinoma
  • Urothelial carcinoma
  • Colorectal cancer
  • Gastric cancer
  • Gastroesophageal junction cancer
  • Esophageal adenocarcinoma
🇨🇦
Approved in Canada as Opdivo for:
  • Melanoma
  • Non-small cell lung cancer
  • Renal cell carcinoma
  • Hodgkin lymphoma
  • Head and neck squamous cell carcinoma
  • Urothelial carcinoma
  • Colorectal cancer
  • Gastric cancer
  • Gastroesophageal junction cancer
  • Esophageal adenocarcinoma
🇨🇭
Approved in Switzerland as Opdivo for:
  • Melanoma
  • Non-small cell lung cancer
  • Renal cell carcinoma
  • Hodgkin lymphoma
  • Head and neck squamous cell carcinoma
  • Urothelial carcinoma
  • Colorectal cancer
  • Gastric cancer
  • Gastroesophageal junction cancer
  • Esophageal adenocarcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials
2,027
Recruited
2,353,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Human cytomegalovirus (CMV) is found in glioblastoma (GBM) tumors but not in normal brain tissue, suggesting that CMV antigens could be effective targets for immunotherapy.
Research shows that T cells specific to the CMV pp65 antigen can recognize and kill GBM tumor cells derived from patients, supporting the potential for CMV-targeted immunotherapies in treating GBM.
Immunological targeting of cytomegalovirus for glioblastoma therapy.Nair, SK., Sampson, JH., Mitchell, DA.[2021]
DCVax-Brain, a personalized treatment using dendritic cells to target brain tumors, shows promise in inducing antitumor immunity with low toxicity in patients with glioblastoma multiforme (GBM).
Recent trials indicate that DC vaccine therapy correlates with clinical improvements in GBM patients, although some reports suggest possible selection bias in the findings.
DCVax-Brain and DC vaccines in the treatment of GBM.Wheeler, CJ., Black, KL.[2019]
Certain high-risk groups, such as HIV-infected individuals, transplant patients, and newborns, are particularly vulnerable to diseases caused by human cytomegalovirus (CMV), highlighting the need for effective vaccination strategies.
While there are currently no licensed CMV vaccines for humans, various vaccine approaches, including protein subunit, DNA, and live attenuated vaccines, are being tested in clinical trials, showing promise in inducing protective immune responses against CMV.
Progress toward an elusive goal: current status of cytomegalovirus vaccines.Schleiss, MR., Heineman, TC.[2007]

References

Immunological targeting of cytomegalovirus for glioblastoma therapy. [2021]
Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells. [2021]
Human cytomegalovirus-based immunotherapy to treat glioblastoma: Into the future. [2021]
Cytomegalovirus as a novel target for immunotherapy of glioblastoma multiforme. [2022]
DCVax-Brain and DC vaccines in the treatment of GBM. [2019]
Progress toward an elusive goal: current status of cytomegalovirus vaccines. [2007]
Intratumoral infection by CMV may change the tumor environment by directly interacting with tumor-associated macrophages to promote cancer immunity. [2018]
Demarcated thresholds of tumor-specific CD8 T cells elicited by MCMV-based vaccine vectors provide robust correlates of protection. [2020]
Desirability and feasibility of a vaccine against cytomegalovirus. [2022]
Cytomegalovirus Enterocolitis in a Patient with Refractory Immune-Related Colitis. [2020]
11.United Statespubmed.ncbi.nlm.nih.gov
A novel cancer vaccine for melanoma based on an approved vaccine against measles, mumps, and rubella. [2022]
Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. [2022]
Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. [2021]
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